|Budget Amount *help
¥14,900,000 (Direct Cost : ¥14,900,000)
Fiscal Year 2004 : ¥5,700,000 (Direct Cost : ¥5,700,000)
Fiscal Year 2003 : ¥9,200,000 (Direct Cost : ¥9,200,000)
We studied relevant host molecular targets utilized for acquisition of HIV infection using a skin explant model system. HIV_<BaL> was applied to the abraded epidermal surface of skin explants. After 3 days, emigrant cells from skin explants were co-cultured with allogeneic T cells. HIV p24 levels in culture supernatants were monitored by ELISA. Interestingly, preincubation of skin explants with PSC-RANTES completely blocked subsequent HIV transmission from emigrant cells to T cells, whereas mannan did not. Strikingly, when infection levels of single LC or DC within emigrant cells were determined, HIV p24+ cells were detected only in LC, but not in DC. To test whether HIV could replicate within LC, skin explants were exposed to HIV variants that were engineered to express GFP during productive infection of cells. HLA-DR+/ Langerin+/ GFP+ emigrated cells were detected in LC-T cell conjugates, when a CCR5-using HIV isolate, but not a CXCR4-using HIV isolate, was applied to skin. Thus, CCR5-mediated productive HIV infection of LC, and not C-type lectin-mediated capture of virus by DC, may provide a biologic basis for understanding susceptibility to initial infection by CCR5-using strains of HIV in humans.